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OBJECTIVE: The activities and products of carbohydrate metabolism are involved in key processes of cancer. However, its relationship with hepatocellular carcinoma (HCC) is unclear. METHODS: The cancer genome atlas (TCGA)-HCC and ICGC-LIRI-JP datasets were acquired via public databases. Differentially expressed genes (DEGs) between HCC and control samples in the TCGA-HCC dataset were identified and overlapped with 355 carbohydrate metabolism-related genes (CRGs) to obtain differentially expressed CRGs (DE-CRGs). Then, univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses were applied to identify risk model genes, and HCC samples were divided into high/low-risk groups according to the median risk score. Next, gene set enrichment analysis (GSEA) was performed on the risk model genes. The sensitivity of the risk model to immunotherapy and chemotherapy was also explored. RESULTS: A total of 8 risk model genes, namely, G6PD, PFKFB4, ACAT1, ALDH2, ACYP1, OGDHL, ACADS, and TKTL1, were identified. Moreover, the risk score, cancer status, age, and pathologic T stage were strongly associated with the prognosis of HCC patients. Both the stromal score and immune score had significant negative/positive correlations with the risk score, reflecting the important role of the risk model in immunotherapy sensitivity. Furthermore, the stromal and immune scores had significant negative/positive correlations with risk scores, reflecting the important role of the risk model in immunotherapy sensitivity. Eventually, we found that high-/low-risk patients were more sensitive to 102 drugs, suggesting that the risk model exhibited sensitivity to chemotherapy drugs. The results of the experiments in HCC tissue samples validated the expression of the risk model genes. CONCLUSION: Through bioinformatic analysis, we constructed a carbohydrate metabolism-related risk model for HCC, contributing to the prognosis prediction and treatment of HCC patients.
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Carbohydrate Metabolism , Carcinoma, Hepatocellular , Liver Neoplasms , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/genetics , Liver Neoplasms/immunology , Humans , Prognosis , Carbohydrate Metabolism/genetics , Gene Expression Regulation, Neoplastic , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Male , Female , Middle Aged , Gene Expression ProfilingABSTRACT
BACKGROUND: Recently, a submucosal trans-septal suturing (STSS) technique was introduced to obviate the dead space of septum after septal extension graft (SEG) with porous high-density polyethylene (pHDPE). OBJECTIVE: To investigate STSS technique after SEG with pHDPE and concurrent nasal lateral osteotomy (LO). METHODS: A retrospective study was conducted in 53 patients who underwent a STSS technique after SEG with pHDPE and concurrent LO. The postoperative discomfort (nasal pain and obstruction), the width of the nasal bony base, Nasal Obstruction Symptom Evaluation (NOSE), Rhinoplasty Outcomes Evaluation (ROE), and complications were recorded and assessed. RESULTS: The mean surgical duration of STSS was 862.53±227.73 seconds. The maximal mean score of postoperative nasal pain and nasal obstruction was 2.132±0.921 and 1.868±0.8995, respectively. The values on the width of the nasal bony base and ROE were significantly improved after surgery. There was no significant difference in NOSE values preoperatively versus 6 months postoperatively. An infection was found in 1 patient, a recurrent minor bleeding of septum in another patient, and a symptomatic nasal obstruction in other 2 patients. There was no major bleeding, hematoma, foreign body sensation, septal perforation, and other infection. CONCLUSION: STSS can eliminate the postoperative dead space of nasal septum with low discomfort and complications, and help to avoid a lateral displacement of osteotomized nasal bony segment (ONBS) in patients undergoing SEG with pHDPE and concurrent LO.
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The development of novel metal-organic frameworks (MOFs) as efficient photocatalysts for hydrogen peroxide production from water and oxygen is particularly interesting, yet remains a challenge. Herein, we have prepared four cyclic trinuclear units (CTUs) based MOFs, exhibiting good light absorption ability and suitable band gaps for photosynthesis of H2O2. However, Cu-CTU-based MOFs are not able to photocatalyzed the formation of H2O2, while the alteration of metal nodes from Cu-CTU to Ag-CTU dramatically enhances the photocatalytic performance for H2O2 production and the production rates can reach as high as 17476â µmol g-1 h-1 with an apparent quantum yield of 4.72 %, at 420â nm, which is much higher than most reported MOFs. The photocatalytic mechanism is comprehensively studied by combining the isotope labeling experiments and DFT calculation. This study provides new insights into the preparation of MOF photocatalysts with high activity for H2O2 production through molecular engineering.
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BACKGROUND: Porous high-density polyethylene (pHDPE) is an alternative material for a septal extension graft (SEG) in oriental rhinoplasty when autologous cartilage is limited. Although nasal packing (NP) and trans-septal suturing (TSS) techniques are routine procedures to obviate the dead space after septoplasty, they are associated with certain discomforts and complications. OBJECTIVE: To investigate the application of a submucosal trans-septal suturing (STSS) technique after SEG with pHDPE. METHODS: A prospective study was conducted on 60 female participants who underwent SEG with pHDPE. The participants were randomly divided into the NP group and STSS group. The extra surgical duration of NP and STSS, pain, nasal obstruction, and sleeping disturbance as well as postoperative complications were recorded and compared between groups. RESULTS: No significant difference was found between group NP and group STSS in terms of mean age. The mean extra surgical duration of group STSS was significantly longer than group NP. There were significant higher pains of group NP at 24 hours and 48 hours postoperatively, compared with group STSS. The NP group also experienced significantly more nasal obstruction and sleep disturbance within 48h postoperatively compared to the STSS group. There was one infection in each group, minor bleeding in two NP patients, and one STSS patient. There was no major bleeding, hematoma, graft exposure, or septal perforation in both groups. CONCLUSION: Although STSS needs a longer extra surgical duration than NP, it significantly improves the patient's postoperative comfort with a faster return to normal respiration compared to NP. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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A novel synthetic approach to preparing alkenyl nitriles via the olefination of aldehydes with diazoacetonitrile catalyzed by iron(II) phthalocyanine in the presence of PPh3 has been developed. A broad variety of aldehydes are efficiently transformed into the corresponding products with the high yields of 75%-97%. And it is also suitable for its gram-scale preparation. The suggested mechanism involves the transformation of the phosphazine to ylide by iron(II) phthalocyanine.
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The construction of stable copper nanoclusters (Cu-NCs) with near-infrared (NIR) emission that can be used for catalysis is highly desired, yet remains a challenge. Herein, an atomically precise bimetallic Cu/Pd NC with a molecular formula of Cu16Pd1L10(PPh3)2(Pz)6 (Pz = 3,5-(CF3)2Pyrazolate, L = 4-CH3OPhC≡C-), abbreviated as Cu16Pd1, is synthesized. Single-crystal X-ray crystallographic analysis of Cu16Pd1 reveals a Cu10Pd1 kernel with pseudo-gyroelongated square bipyramid confirmation surrounded by other 6 Cu(I) ions and protected ligands. Interestingly, it exhibits strong NIR emission with the highest photoluminescence quantum yield (PLQY) among all the Cu NCs/Cu alloys (λem > 800 nm) in the solid-state, and also displays NIR emission in solution. Experimental results and theoretical calculations suggest that the impressive NIR emission is attributed to abundant supramolecular interactions in the solid-state, including intramolecular metal-metal and intermolecular interactions. Of note, the bimetallic Cu16Pd1 can catalyze the reduction of 4-nitrophenol. This work provides a novel method for synthesizing Cu/Pd NCs and reminds that the less studied Cu/Pd NC can serve as outstanding luminescent material, which is seldom noticed in atomically precise nanoclusters.
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Objective To establish a low density, high purity and high stability in vitro culture method of primary hippocampal neurons of fetal rats by co-culturing hippocampal and cortical cells, so as to obtain higher purity and better vitality of primary hippocampal neurons disease. Methods The fetal rat hippocampal tissue was isolated from 16-18 days pregnant SD rats, then cut and digested by 0.125% trypsin. The obtained cell suspension was filtered by 200 mesh cell sieve, and then the obtained cell suspensions were then inoculated into the inner layer and outer ring of the culture plate in a surrounding form. They were co-cultured in DMEM/F12 medium containing 10% horse serum. After 4-6 hours of cell adhesion, the culture medium was changed to maintenance medium (Neurobasal+2% B27+0.5 mmol/L glutamine). Then the cell viability was detected with CCK-8 kit and the purity of hippocampal neurons was detected by immunofluorescent staining. Results Hippocampal neurons grew well and formed crisscross neural networks after 5 days. And it could survive for 3 weeks. The purity of hippocampal neurons was up to 98%. Conclusion The method of co-culturing hippocampal and cortical cells can obtain high-purity, high activity, high survival rate, and high stability primary hippocampal neurons from fetal rats, which can provide certain experimental conditions for the study of hippocampal neuron related diseases in the nervous system and is worthy of promotion and application.
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BACKGROUND: Climate change profoundly shapes the population health at the global scale. However, there was still insufficient and inconsistent evidence for the association between heat exposure and chronic kidney disease (CKD). METHODS: In the present study, we studied the association of heat exposure with hospitalizations for cause-specific CKD using a national inpatient database in China during the study period of hot season from 2015 to 2018. Standard time-series regression models and random-effects meta-analysis were developed to estimate the city-specific and national averaged associations at a 7 lag-day span, respectively. RESULTS: A total of 768,129 hospitalizations for CKD was recorded during the study period. The results showed that higher temperature was associated with elevated risk of hospitalizations for CKD, especially in sub-tropical cities. With a 1 °C increase in daily mean temperature, the cumulative relative risks (RR) over lag 0-7 d were 1.008 [95% confidence interval (CI) 1.003-1.012] for nationwide. The attributable fraction of CKD hospitalizations due to high temperatures was 5.50%. Stronger associations were observed among younger patients and those with obstructive nephropathy. Our study also found that exposure to heatwaves was associated with added risk of hospitalizations for CKD compared to non-heatwave days (RR = 1.116, 95% CI 1.069-1.166) above the effect of daily mean temperature. CONCLUSIONS: Short-term heat exposure may increase the risk of hospitalization for CKD. Our findings provide insights into the health effects of climate change and suggest the necessity of guided protection strategies against the adverse effects of high temperatures.
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Hot Temperature , Renal Insufficiency, Chronic , Humans , China , Cities , Hospitalization , Time FactorsABSTRACT
Realizing high photoluminescence quantum yield (PLQY) in the near-infrared (NIR) region is challenging and valuable for luminescent material, especially for thermally activated delay fluorescence (TADF) material. In this work, we report two achiral cyclic trinuclear Au(I) complexes, Au3 (4-Clpyrazolate)3 and Au3 (4-Brpyrazolate)3 (denoted as Cl-Au and Br-Au), obtained through the reaction of 4-chloro-1H-pyrazole and 4-bromo-1H-pyrazole with Au(I) salts, respectively. Both Cl-Au and Br-Au exhibit TADF with high PLQY (>70 %) in the NIR I (700-900â nm) (λmax = 720â nm) region, exceeding other NIR-TADF emitters in the solid state. Photophysical experiments and theoretical calculations confirmed the efficient NIR-TADF properties of Cl-Au and Br-Au were attributed to the small energy gap ΔE(S1-T2) (S = singlet, T = triplet) and the large spin-orbital coupling induced by ligand-to-metal-metal charge transfer of molecular aggregations. In addition, both complexes crystallize in the achiral Pna21 space group (mm2 point group) and are circularly polarized light (CPL) active with maxima luminescent dissymmetry factor |glum | of 3.4 × 10-3 (Cl-Au) and 2.7 × 10-3 (Br-Au) for their crystalline powder samples, respectively. By using Cl-Au as the emitting ink, 3D-printed luminescent logos are fabricated, which own anti-counterfeiting functions due to its CPL behavior dependent on the crystallinity.
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Protein-polyphenol colloidal particles are promising stabilizers for high internal phase Pickering emulsions (HIPPEs). However, the relationship between the structure of the polyphenols and its ability to stabilize HIPPEs has not been studied thus far. In this study, bovine serum albumin (BSA)-polyphenols (B-P) complexes were prepared, and their ability to stabilize HIPPEs was investigated. The polyphenols were bound to BSA via non-covalent interactions. Optically isomeric polyphenols formed similar bonds with BSA, whereas a greater number of trihydroxybenzoyl groups or hydroxyl groups in the dihydroxyphenyl moieties of polyphenols increased the B-P interactions. Polyphenols also reduced the interfacial tension and enhanced the wettability at the oil-water interface. The HIPPE stabilized by BSA-tannic acid complex exhibited the highest stability among the B-P complexes and resisted demixing and aggregation during centrifugation. This study promotes the potential applications of polyphenol-protein colloidal particles-stabilized HIPPEs in the food industry.
Subject(s)
Polyphenols , Tannins , Polyphenols/chemistry , Emulsions/chemistry , Tannins/chemistry , Wettability , Particle SizeABSTRACT
Porous high-density polyethylene (pHDPE) is an alternative material for septal extension grafts. This study investigated the clinical application of a single T-shaped pHDPE graft combined with auricular cartilage in oriental nasal tip-plasty. A retrospective analysis was conducted of 66 patients who underwent septal extension graft with a T-shaped pHDPE and auricular cartilage graft from December 2018 to November 2021. All patients were female from 19 to 51 years old (average: 28.9 years). Patients were followed up for 5 to 40 months with an average of 23.8 months. The postoperative nasal length (39.8±3.7 mm) was significantly improved (35.6±5.7 mm preoperatively, P <0.0001) with the tip projection increasing from 23.9±2.3 mm preoperatively to 25.3±2.4 mm postoperatively ( P =0.0005). There was a significant difference in the nasolabial angle (96.8±14.1 degrees preoperatively versus 101.8±7.2 degrees postoperatively, P =0.0105) but no significant change in the nasofrontal angle (143.3±9.5 degrees preoperatively versus 143.7±5.5 degrees postoperatively, P =0.7546), with an improved tip projection achieved in 93.9% of patients. One patient had an abscess in the nasal septum and a tip graft was performed using auricular cartilage in another patient because of an insufficient postoperative tip projection. There was a slight tip deviation in 2 patients, 1 case of a deviated nasal tip was corrected with a pHDPE sheet graft, while the other was left intact. Two patients had excess cartilaginous graft protruding to the nasal cavity that did not affect nasal ventilation and the shape of the nasal tip was relatively good, so the prominent cartilaginous graft was not addressed. In conclusion, this technique not only improved the bulbous nasal tip, lengthened the short nose, and increase the tip projection, but also prevented absorption of the existing septal cartilage and reduced infection or extrusion of the pHDPE.
Subject(s)
Nasal Septum , Polyethylene , Rhinoplasty , Adult , Female , Humans , Male , Middle Aged , Young Adult , Esthetics, Dental , Nasal Cartilages/transplantation , Nasal Septum/surgery , Nose/surgery , Porosity , Retrospective Studies , Rhinoplasty/methods , Treatment OutcomeABSTRACT
Chrysanthemum waste (CW) is an agricultural and industrial by-product produced during chrysanthemum harvesting, drying, preservation, and deep processing. Although it is nutritious, most CW is discarded, wasting resources and contributing to serious environmental problems. This work explored a solid-state fermentation (SSF) strategy to improve CW quality for use as an alternative feed ingredient. Orthogonal experiment showed that the optimal conditions for fermented chrysanthemum waste (FCW) were: CW to cornmeal mass ratio of 9:1, Pediococcus cellaris + Candida tropicalis + Bacillus amyloliquefaciens proportions of 2:2:1, inoculation amount of 6%, and fermentation time of 10 d. Compared with the control group, FCW significantly increased the contents of crude protein, ether extract, crude fiber, acid detergent fiber, neutral detergent fiber, ash, calcium, phosphorus, and total flavonoids (p < 0.01), and significantly decreased pH and saponin content (p < 0.01). SSF improved the free and hydrolyzed amino acid profiles of FCW, increased the content of flavor amino acids, and improved the amino acid composition of FCW protein. Overall, SSF improved CW nutritional quality. FCW shows potential use as a feed ingredient, and SSF helps reduce the waste of chrysanthemum processing.
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Amino Acids , Detergents , Fermentation , Starch , Animal Feed/analysisABSTRACT
Objective:To observe any effect of ultrashortwave (USW) therapy on inflammatory cytokines and the MAPK pathway of rats with a spinal cord injury.Methods:Seventy-nine Sprague-Dawley rats were randomly divided into a control group ( n=35), an intervention group ( n=35) and a sham group ( n=9). Allen′s method was used to establish a contusion model of SCI in the rats of the control and intervention groups, while the sham group′s spinal tissues were exposed but not stricken. Beginning twenty-four hours after SCI modeling, the intervention group was given 7min of USW therapy daily, five days a week till the day of sacrifice for sampling the target area of spinal cord for tests. Then, motion function was evaluated using Basso, Beattie and Bresnahan (BBB) scoring. One, three and seven days after the SCI modeling, immunofluorescence and western blotting were employed to observe any changes in inflammatory factors and the MAPK pathway in the lesioned area. Results:Fourteen days after the modeling the average BBB score of the intervention group was significantly higher than the control group′s average. Moreover, 7 days after the modeling the average content of the domains containing protein 3 (NLRP3), interleukin-6 (IL-6), IL-6 receptor and tumor necrosis factor-α (TNF-α) in the target area of the spinal cord of sham group showed significantly lower levels than in the other 2 groups. And the levels in the intervention group were significantly lower than in the control group. Seven days after the modeling the number of cells positive for zinc finger protein 36 (TTP) in the lesioned area of the intervention group was significantly greater than among the control group. At the same time the levels of MAPK-activated protein kinase 2 (MK2), phosphorylated-mitogen-activated protein kinase-activated version (p-MK2) and TTP in the control and intervention groups were significantly higher than in the sham group. And there were significant differences between the intervention group and control group in the levels of MK2, p-MK2 and TTP.Conclusion:Ultrashortwave therapy can inhibit inflammation by regulating the MAPK inflammatory pathway, promoting the recovery of motion functions, at least in rats.
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Objective:To explore the feasibility of smart phone real-time picture exchange-assisted telecytopathology for rapid on-site evaluation (tele-ROSE), and the role of tele-ROSE in improving the diagnostic efficiency of endoscopic physicians.Methods:Data of patients who underwent endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) from April 2020 to May 2021 in Qilu Hospital of Shandong University were retrospectively collected. Patients who didn't receive ROSE from April 2020 to October 2020 were enrolled in the non-ROSE group, and those who underwent ROSE from November 2020 to May 2021 were enrolled in the ROSE group, of which endosonographers used WeChat on the smartphone to send ROSE images to cytopathologists from November 2020 to March 2021 were the mobile phone group, and those whose ROSE results independently diagnosed by trained endosonographers from April 2021 to May 2021 were the self-ROSE group. Basic information, ROSE results, postoperative pathology and follow-up were compared, and the diagnostic effectiveness of tele-ROSE was analyzed.Results:A total of 188 cases were included, of which 179 cases (95.2%) were solid pancreatic lesions and 9 (4.8%) were enterocoelia lesions. There was no significant difference in the puncture time among the non-ROSE, mobile phone and self-ROSE groups [3 (3, 4) VS 3 (3, 4) VS 3 (2, 4), H=1.320, P=0.517]. With the final diagnosis as the golden standard, the sensitivity, the specificity, the accuracy, the positive predictive value, the negative predictive value and Kappa value of the non-ROSE group were 80.6% (58/72), 89.5% (17/19), 82.4% (75/91), 96.7% (58/60), 54.8% (17/31), and 0.6 respectively. The corresponding indices in the ROSE group were 97.4% (74/76), 100.0% (21/21), 97.9% (95/97), 100.0% (74/74), 91.3% (21/23), and 0.9 respectively, those of the mobile phone group were 95.2% (40/42), 100.0% (10/10), 96.2% (50/52), 100.0% (40/40), 83.3% (10/12), and 0.9 respcetively, and those of the self-ROSE group were 100.0% (34/34), 100.0% (11/11), 100.0% (45/45), 100.0% (34/34), 100.0% (11/11), and 1.0 respectively. The sensitivity ( P=0.002), the accuracy ( P=0.001) and the negative predictive value ( P=0.009) of the ROSE group were significantly higher than those of the non-ROSE group, and there was no significant difference in other diagnostic efficacy indices ( P>0.05). There was no significant difference between the mobile phone group and the self-ROSE group in diagnostic efficacy ( P>0.05). Conclusion:Instant smartphone-assisted tele-ROSE through WeChat can well meet the needs of pathologists and endoscopic physicians. After the application of tele-ROSE training, the diagnostic accuracy of endoscopic physicians is equivalent to that of cytopathologist, which helps to obtain more sufficient specimens under endoscopy and improve the diagnostic accuracy of EUS-FNA.
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Objective:To investigate the clinical application of Grunenwald incision in cervicothoracic junction surgery.Methods:The clinical data of 25 patients with cervicothoracic junction tumor and 1 patient with cervicothoracic junction trauma in the single treatment group of Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University from December 2011 to September 2021 were analyzed retrospectively, including 19 males and 7 females, aged 9-73 years old. Among the 26 patients, there were 9 cases of upper mediastinal tumor, 6 cases of superior sulcus tumor, 4 cases of thyroid tumor invading the upper mediastinal, 4 cases of chest wall tumor, 2 cases of esophageal cancer combined with supraclavicular lymph node metastasis, and 1 case of foreign body penetrating injury at the cervicothoracic junction. Grunenwald incision or additional posterolateral thoracic incision, median sternal incision, neck collar incision were used in all patients. The degree of tumor resection was evaluated. The operation time, intraoperative blood loss, length of hospital stay were observed, and the postoperative follow-up was analyzed.Results:There was no perioperative death in the whole group. 14 cases were treated with Grunenwald incision alone, 6 cases with additional posterolateral chest incision, 4 cases with additional neck collar incision, and 2 cases with additional median sternal incision. The tumors were completely resection in 22 cases, palliative tumor resection in 3 cases, and complete foreign body removal in 1 case. Postoperative pathology included 4 cases of schwannoma; 3 cases of lung adenocarcinoma, thyroid cancer and myofibroblastoma, respectively; 2 cases of supraclavicular lymph node metastasis of esophageal cancer and lung squamous carcinoma, respectively; 1 case of large cell neuroendocrine carcinoma, metastatic carcinoma of the first rib after lung squamous cell carcinoma, ganglioneuroma, nodular goiter, hemangioma, well differentiated liposarcoma, vascular endothelial tumor and cavernous angioma, respectively. The operation time was 120-430 min, with a mean of(226.92±88.40)min. The intraoperative blood loss was 100-1 000 ml, with a mean of(273.46±196.34)ml. The length of hospital stay was 6-26 days, with a mean of(12.73±4.46 )days. 26 patients were followed up for 6-130 months, with a mean of(57.88±43.64) months. During the follow-up period, 6 patients died.Conclusion:Grunenwald incision can provide good exposure of the structures near the cervicothoracic junction, preserve the integrity of sternoclavicular joint, reduce shoulder deformity, and has advantages for patients with cervicothoracic junction tumors, high rib resection, and cervicothoracic junction trauma.
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A complex pathophysiological mechanism is involved in brain injury following cerebral infarction. The neurovascular unit (NVU) is a complex multi-cellular structure consisting of neurons, endothelial cells, pericyte, astrocyte, microglia and extracellular matrix, etc. The dyshomeostasis of NVU directly participates in the regulation of inflammatory immune process. The components of NVU promote inflammatory overreaction and synergize with the overactivation of autonomic nervous system to initiate stroke-induced immunodepression (SIID). SIID can alleviate the damage caused by inflammation, however, it also makes stroke patients more susceptible to infection, leading to systemic damage. This article reviews the mechanism of SIID and the roles of NVU in SIID, to provide a perspective for reperfusion, prognosis and immunomodulatory therapy of cerebral infarction.
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Humans , Endothelial Cells , Stroke , Neurons/physiology , Immunosuppression Therapy/adverse effects , Cerebral InfarctionABSTRACT
A complex pathophysiological mechanism is involved in the brain injury following cerebral infarction. The neurovascular unit (NVU) is a complex multi-cellular structure consisting of endothelial cells , neurons, glia, smooth muscle cells, and pericytes. The dyshomeostasis of NVU directly participates in the inflammatory immune regulation process. The components of NVU promote inflammatory overreaction and also synergize with the overactivation of autonomic nervous system to initiate stroke-induced immunosuppression (SIID). SIID can alleviate the damage caused by inflammation, however, it also makes stroke patients more susceptible to infection, leading to systemic damage and worsening the condition. This article reviews the mechanism of SIID and the roles of NVU components in SIID, to provide a perspective for recanalization, prognosis and immune regulation therapy of cerebral infarction.
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Background: Long term high fat diets (HFD) promote skin aging pathogenesis, but detailed mechanisms remain unclear especially for inflammaging, which has recently emerged as a pathway correlating aging and age-related disease with inflammation. p16INK4a (hereafter termed p16) inhibits the cell cycle, with p16 deletion significantly inhibiting inflammaging. We observed that HFD-induced p16 overexpression in the skin. Therefore, we investigated if p16 exacerbated inflammaging in HFD-induced skin and also if p16 deletion exerted protective effects against this process. Methods: Eight-week-old double knockout (KO) ApoE-/-p16-/- mice and ApoE-/- littermates were fed HFD for 12 weeks and their skin phenotypes were analyzed. We measured skin fibrosis, senescence-associated secretory phenotype (SASP) levels, and integrin-inflammasome pathway activation using histopathological, RNA-sequencing (RNA-seq), bioinformatics analysis, and molecular techniques. Results: We found that HFD contributed to inflammaging in the skin by activating the NLRP3 inflammasome pathway, increasing inflammatory infiltration, and promoting apoptosis by balancing expression between proapoptotic and antiapoptotic molecules. p16 knockout, when compared with the ApoE-/- phenotype, inhibited skin fibrosis by ameliorating inflammatory infiltration and proinflammatory factor expression (Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)), and also alleviated inflammaging skin progress induced by HFD in the ApoE-/- mouse model. RNA-seq showed that p16 KO mice inhibited both integrin-inflammasome and NF-κB proinflammatory pathway activation. Conclusions: p16 deletion or p16 positive cell clearance could be a novel strategy preventing long term HFD-induced skin aging.
Subject(s)
Cyclin-Dependent Kinase Inhibitor p16 , Diet, High-Fat , Skin Diseases , Animals , Mice , Cyclin-Dependent Kinase Inhibitor p16/genetics , Diet, High-Fat/adverse effects , Fibrosis , Inflammasomes , Interleukin-6 , Mice, Knockout, ApoE , Skin Diseases/genetics , Skin/pathologyABSTRACT
The past twenty years have seen the increasingly important role of ontology in traditional Chinese medicine (TCM). However, the development of TCM ontology faces many challenges. Since the epistemologies dramatically differ between TCM and contemporary biomedicine, it is hard to apply the existing top-level ontology mechanically. "Data silos" are widely present in the currently available terminology standards, term sets, and ontologies. The formal representation of ontology needs to be further improved in TCM. Therefore, we propose a unified basic semantic framework of TCM based on in-depth theoretical research on the existing top-level ontology and a re-study of important concepts in TCM. Under such a framework, ontologies in TCM sub-domains should be built collaboratively and be represented formally in a common format. Besides, extensive cooperation should be encouraged by establishing ontology research communities to promote ontology peer review and reuse.
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Drugs, Chinese Herbal , Medicine, Chinese Traditional , SemanticsABSTRACT
The Nod-like receptor (NLR) family CARD domain containing 5 (NLRC5) has been reported as an activator of human leukocyte antigen (HLA) class I that is responsible for immune activity in cancer treatment. This work focuses on the role of BMI1 proto-oncogene (BMI1) in the NLRC5-HLA class I axis and in immune escape in non-small cell lung cancer (NSCLC). First, immunoblot analysis and/or reverse transcription-quantitative polymerase chain reaction were performed, which identified decreased NLRC5 and HLA class I levels in NSCLC tissues and cell lines. NSCLCs were co-cultured with activated CD8+ T cells. Overexpression of NLRC5 in NSCLC cells elevated the expression of HLA class I and increased the activity of T cells and IL-2 production, and it reduced the PD-1/PD-L1 levels. The ubiquitination and immunoprecipitation assays confirmed that BMI1 bound to NLRC5 to induce is ubiquitination and protein degradation. Downregulation of BMI1 in NSCLC cells elevated NLRC5 and HLA class I levels, and consequently promoted T cell activation and decreased PD-1/PD-L1 levels in the co-culture system. However, overexpression of BMI1 in cells led to inverse trends. In summary, this study demonstrates that BMI1 induces ubiquitination and protein degradation of NLRC5 and suppresses HLA class I expression, which potentially helps immune escape in NSCLC.